Skip to main content
Erschienen in: Cancer Immunology, Immunotherapy 6/2013

01.06.2013 | Original Article

Long-term survival and immunological parameters in metastatic melanoma patients who responded to ipilimumab 10 mg/kg within an expanded access programme

verfasst von: Anna Maria Di Giacomo, Luana Calabrò, Riccardo Danielli, Ester Fonsatti, Erica Bertocci, Isabella Pesce, Carolina Fazio, Ornella Cutaia, Diana Giannarelli, Clelia Miracco, Maurizio Biagioli, Maresa Altomonte, Michele Maio

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 6/2013

Einloggen, um Zugang zu erhalten

Abstract

Background

Ipilimumab can result in durable clinical responses among patients with advanced melanoma. However, no predictive marker of clinical activity has yet been identified. We provide preliminary data describing the correlation between immunological parameters and response/survival among patients with advanced melanoma who received ipilimumab 10 mg/kg in an expanded access programme.

Methods

Patients received ipilimumab 10 mg/kg every 3 weeks (Q3W) for four doses (induction) and Q12W from week 24 (W24) as maintenance therapy. Tumor assessments were conducted Q12W. Expression of inducible T cell costimulator (ICOS) on CD4+ and CD8+ T cells was assessed at baseline, W7, W12 and W24, and the ratio between absolute neutrophils (N) and lymphocytes (L) determined at baseline, W4, W7 and W10.

Results

Median overall survival among 27 patients was 9.6 months (95 % CI 3.2–16.1), with 3- and 4-year survival rates of 20.4 %. Five patients survived >4 years. Patients with an increase in the number of circulating ICOS+ T cells at W7 were more likely to experience disease control and have improved survival. An N/L ratio below the median at W7 and W10 was also associated with better survival compared with an N/L ratio above the median.

Conclusions

Ipilimumab can induce long-term survival benefits in heavily pretreated patients with metastatic melanoma. Changes in the number of circulating ICOS+ T cells or N/L ratio during ipilimumab treatment may represent early markers of response. However, given the limited sample size, further investigation is required.
Literatur
1.
Zurück zum Zitat Ferlay J, Parkin DM, Steliarova-Foucher E (2010) Estimates of cancer incidence and mortality in Europe in 2008. Eur J Cancer 46:765–781PubMedCrossRef Ferlay J, Parkin DM, Steliarova-Foucher E (2010) Estimates of cancer incidence and mortality in Europe in 2008. Eur J Cancer 46:765–781PubMedCrossRef
2.
Zurück zum Zitat Jemal A, Siegel R, Xu J, Ward E (2010) Cancer statistics, 2010. CA Cancer J Clin 60:277–300PubMedCrossRef Jemal A, Siegel R, Xu J, Ward E (2010) Cancer statistics, 2010. CA Cancer J Clin 60:277–300PubMedCrossRef
3.
Zurück zum Zitat Korn EL, Liu PY, Lee SJ, Chapman JA, Niedzwiecki D, Suman VJ, Moon J, Sondak VK, Atkins MB, Eisenhauer EA, Parulekar W, Markovic SN, Saxman S, Kirkwood JM (2008) Meta-analysis of phase II cooperative group trials in metastatic stage IV melanoma to determine progression-free and overall survival benchmarks for future phase II trials. J Clin Oncol 26:527–534PubMedCrossRef Korn EL, Liu PY, Lee SJ, Chapman JA, Niedzwiecki D, Suman VJ, Moon J, Sondak VK, Atkins MB, Eisenhauer EA, Parulekar W, Markovic SN, Saxman S, Kirkwood JM (2008) Meta-analysis of phase II cooperative group trials in metastatic stage IV melanoma to determine progression-free and overall survival benchmarks for future phase II trials. J Clin Oncol 26:527–534PubMedCrossRef
4.
Zurück zum Zitat Tarhini AA, Agarwala SS (2006) Cutaneous melanoma: available therapy for metastatic disease. Dermatol Ther 19:19–25PubMedCrossRef Tarhini AA, Agarwala SS (2006) Cutaneous melanoma: available therapy for metastatic disease. Dermatol Ther 19:19–25PubMedCrossRef
5.
Zurück zum Zitat Eggermont AM (2010) Advances in systemic treatment of melanoma. Ann Oncol 21(Suppl 7):vii339–vii344PubMedCrossRef Eggermont AM (2010) Advances in systemic treatment of melanoma. Ann Oncol 21(Suppl 7):vii339–vii344PubMedCrossRef
6.
Zurück zum Zitat Serrone L, Zeuli M, Sega FM, Cognetti F (2000) Dacarbazine-based chemotherapy for metastatic melanoma: thirty-year experience overview. J Exp Clin Cancer Res 19:21–34PubMed Serrone L, Zeuli M, Sega FM, Cognetti F (2000) Dacarbazine-based chemotherapy for metastatic melanoma: thirty-year experience overview. J Exp Clin Cancer Res 19:21–34PubMed
7.
Zurück zum Zitat Peggs KS, Quezada SA, Korman AJ, Allison JP (2006) Principles and use of anti-CTLA4 antibody in human cancer immunotherapy. Curr Opin Immunol 18:206–213PubMedCrossRef Peggs KS, Quezada SA, Korman AJ, Allison JP (2006) Principles and use of anti-CTLA4 antibody in human cancer immunotherapy. Curr Opin Immunol 18:206–213PubMedCrossRef
8.
Zurück zum Zitat Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, Akerley W, van den Eertwegh AJ, Lutzky J, Lorigan P, Vaubel JM, Linette GP, Hogg D, Ottensmeier CH, Lebbe C, Peschel C, Quirt I, Clark JI, Wolchok JD, Weber JS, Tian J, Yellin MJ, Nichol GM, Hoos A, Urba WJ (2010) Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 363:711–723PubMedCrossRef Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, Akerley W, van den Eertwegh AJ, Lutzky J, Lorigan P, Vaubel JM, Linette GP, Hogg D, Ottensmeier CH, Lebbe C, Peschel C, Quirt I, Clark JI, Wolchok JD, Weber JS, Tian J, Yellin MJ, Nichol GM, Hoos A, Urba WJ (2010) Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 363:711–723PubMedCrossRef
9.
Zurück zum Zitat Robert C, Thomas L, Bondarenko I, O’Day S, Garbe JWC, Lebbe C, Baurain JF, Testori A, Grob JJ, Davidson N, Richards J, Maio M, Hauschild A, Miller WH Jr, Gascon P, Lotem M, Harmankaya K, Ibrahim R, Francis S, Chen TT, Humphrey R, Hoos A, Wolchok JD (2011) Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med 364:2517–2526PubMedCrossRef Robert C, Thomas L, Bondarenko I, O’Day S, Garbe JWC, Lebbe C, Baurain JF, Testori A, Grob JJ, Davidson N, Richards J, Maio M, Hauschild A, Miller WH Jr, Gascon P, Lotem M, Harmankaya K, Ibrahim R, Francis S, Chen TT, Humphrey R, Hoos A, Wolchok JD (2011) Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med 364:2517–2526PubMedCrossRef
10.
Zurück zum Zitat Hamid O, Schmidt H, Nissan A, Ridolfi L, Aamdal S, Hansson J, Guida M, Hyams DM, Gomez H, Bastholt L, Chasalow SD, Berman D (2011) A prospective phase II trial exploring the association between tumor microenvironment biomarkers and clinical activity of ipilimumab in advanced melanoma. J Transl Med 9:204PubMedCrossRef Hamid O, Schmidt H, Nissan A, Ridolfi L, Aamdal S, Hansson J, Guida M, Hyams DM, Gomez H, Bastholt L, Chasalow SD, Berman D (2011) A prospective phase II trial exploring the association between tumor microenvironment biomarkers and clinical activity of ipilimumab in advanced melanoma. J Transl Med 9:204PubMedCrossRef
11.
Zurück zum Zitat Wang W, Yu D, Sarnaik AA, Yu B, Hall M, Morelli D, Zhang Y, Zhao X, Weber JS (2012) Biomarkers on melanoma patient T cells associated with ipilimumab treatment. J Transl Med 10:146PubMedCrossRef Wang W, Yu D, Sarnaik AA, Yu B, Hall M, Morelli D, Zhang Y, Zhao X, Weber JS (2012) Biomarkers on melanoma patient T cells associated with ipilimumab treatment. J Transl Med 10:146PubMedCrossRef
12.
Zurück zum Zitat Yuan J, Adamow M, Ginsberg BA, Rasalan TS, Ritter E, Gallardo HF, Xu Y, Pogoriler E, Terzulli SL, Kuk D, Panageas KS, Ritter G, Sznol M, Halaban R, Jungbluth AA, Allison JP, Old LJ, Wolchok JD, Gnjatic S (2011) Integrated NY-ESO-1 antibody and CD8 + T-cell responses correlate with clinical benefit in advanced melanoma patients treated with ipilimumab. Proc Natl Acad Sci USA 108:16723–16728PubMedCrossRef Yuan J, Adamow M, Ginsberg BA, Rasalan TS, Ritter E, Gallardo HF, Xu Y, Pogoriler E, Terzulli SL, Kuk D, Panageas KS, Ritter G, Sznol M, Halaban R, Jungbluth AA, Allison JP, Old LJ, Wolchok JD, Gnjatic S (2011) Integrated NY-ESO-1 antibody and CD8 + T-cell responses correlate with clinical benefit in advanced melanoma patients treated with ipilimumab. Proc Natl Acad Sci USA 108:16723–16728PubMedCrossRef
13.
Zurück zum Zitat Di Giacomo AM, Danielli R, Calabro L, Bertocci E, Nannicini C, Giannarelli D, Balestrazzi A, Vigni F, Riversi V, Miracco C, Biagioli M, Altomonte M, Maio M (2011) Ipilimumab experience in heavily pretreated patients with melanoma in an expanded access program at the university hospital of Siena (Italy). Cancer Immunol Immunother 60:467–477PubMedCrossRef Di Giacomo AM, Danielli R, Calabro L, Bertocci E, Nannicini C, Giannarelli D, Balestrazzi A, Vigni F, Riversi V, Miracco C, Biagioli M, Altomonte M, Maio M (2011) Ipilimumab experience in heavily pretreated patients with melanoma in an expanded access program at the university hospital of Siena (Italy). Cancer Immunol Immunother 60:467–477PubMedCrossRef
14.
Zurück zum Zitat Ku GY, Yuan J, Page DB, Schroeder SE, Panageas KS, Carvajal RD, Chapman PB, Schwartz GK, Allison JP, Wolchok JD (2010) Single-institution experience with ipilimumab in advanced melanoma patients in the compassionate use setting: lymphocyte count after 2 doses correlates with survival. Cancer 116:1767–1775PubMedCrossRef Ku GY, Yuan J, Page DB, Schroeder SE, Panageas KS, Carvajal RD, Chapman PB, Schwartz GK, Allison JP, Wolchok JD (2010) Single-institution experience with ipilimumab in advanced melanoma patients in the compassionate use setting: lymphocyte count after 2 doses correlates with survival. Cancer 116:1767–1775PubMedCrossRef
15.
Zurück zum Zitat Simeone E, Gentilcore G, Romano A, Daponte A (2012) Immunological and biological changes during ipilimumab (Ipi) treatment and their correlation with clinical response and survival. J Clin Oncol 30(Suppl): abstract 8573 Simeone E, Gentilcore G, Romano A, Daponte A (2012) Immunological and biological changes during ipilimumab (Ipi) treatment and their correlation with clinical response and survival. J Clin Oncol 30(Suppl): abstract 8573
16.
Zurück zum Zitat Berrocal A, Lopez-Martin JA, Arance AM, Soriano VEE (2012) Spanish experience with the ipilimumab Expanded Access Program. J Clin Oncol 30(Suppl): abstract e19023 Berrocal A, Lopez-Martin JA, Arance AM, Soriano VEE (2012) Spanish experience with the ipilimumab Expanded Access Program. J Clin Oncol 30(Suppl): abstract e19023
17.
Zurück zum Zitat Danielli R, Ridolfi R, Chiarion-Sileni V, Queirolo P, Testori A, Plummer R, Boitano M, Calabro L, Rossi CD, Di Giacomo AM, Ferrucci PF, Ridolfi L, Altomonte M, Miracco C, Balestrazzi A, Maio M (2012) Ipilimumab in pretreated patients with metastatic uveal melanoma: safety and clinical efficacy. Cancer Immunol Immunother 61:41–48PubMedCrossRef Danielli R, Ridolfi R, Chiarion-Sileni V, Queirolo P, Testori A, Plummer R, Boitano M, Calabro L, Rossi CD, Di Giacomo AM, Ferrucci PF, Ridolfi L, Altomonte M, Miracco C, Balestrazzi A, Maio M (2012) Ipilimumab in pretreated patients with metastatic uveal melanoma: safety and clinical efficacy. Cancer Immunol Immunother 61:41–48PubMedCrossRef
18.
Zurück zum Zitat Wilgenhof S, Four SD, Everaert H, Neyns B (2012) Patterns of response in patients with pretreated metastatic melanoma who received ipilimumab 3 mg/kg in a European expanded access program: five illustrative case reports. Cancer Invest 30:712–720PubMedCrossRef Wilgenhof S, Four SD, Everaert H, Neyns B (2012) Patterns of response in patients with pretreated metastatic melanoma who received ipilimumab 3 mg/kg in a European expanded access program: five illustrative case reports. Cancer Invest 30:712–720PubMedCrossRef
19.
Zurück zum Zitat Di Giacomo AM, Calabrò L, Danielli R, Fonsatti E, Bertocci E, Pesce I, Giannarelli D, Biagioli M, Altomonte M, Maio M (2012) Long term survival and immunological correlates in metastatic melanoma treated with ipilimumab at 10 mgs within an expanded access program. Ann Oncol 23(Suppl 9):abstract 1117PD Di Giacomo AM, Calabrò L, Danielli R, Fonsatti E, Bertocci E, Pesce I, Giannarelli D, Biagioli M, Altomonte M, Maio M (2012) Long term survival and immunological correlates in metastatic melanoma treated with ipilimumab at 10 mgs within an expanded access program. Ann Oncol 23(Suppl 9):abstract 1117PD
20.
Zurück zum Zitat Lebbe C, Weinberg AD, Maio M, Neyns B, Harmankaya K, Chin K, Opatt McDowell D, Cykowski L, McHenry MB, Wolchok JD (2012) Five-year survival rates for patients (Pts) with metastatic melanoma (MM) treated with ipilimumab (Ipi) in phase II trials. Ann Oncol 23(Suppl 9):abstract 1116PD Lebbe C, Weinberg AD, Maio M, Neyns B, Harmankaya K, Chin K, Opatt McDowell D, Cykowski L, McHenry MB, Wolchok JD (2012) Five-year survival rates for patients (Pts) with metastatic melanoma (MM) treated with ipilimumab (Ipi) in phase II trials. Ann Oncol 23(Suppl 9):abstract 1116PD
21.
Zurück zum Zitat Prieto PA, Yang JC, Sherry RM, Hughes MS, Kammula US, White DE, Levy CL, Rosenberg SA, Phan GQ (2012) CTLA-4 blockade with ipilimumab: long-term follow-up of 177 patients with metastatic melanoma. Clin Cancer Res 18:2039–2047PubMedCrossRef Prieto PA, Yang JC, Sherry RM, Hughes MS, Kammula US, White DE, Levy CL, Rosenberg SA, Phan GQ (2012) CTLA-4 blockade with ipilimumab: long-term follow-up of 177 patients with metastatic melanoma. Clin Cancer Res 18:2039–2047PubMedCrossRef
22.
Zurück zum Zitat Wolchok JD, Hoos A, O’Day S, Weber JS, Hamid O, Lebbe C, Maio M, Binder M, Bohnsack O, Nichol G, Humphrey R, Hodi FS (2009) Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin Cancer Res 15:7412–7420PubMedCrossRef Wolchok JD, Hoos A, O’Day S, Weber JS, Hamid O, Lebbe C, Maio M, Binder M, Bohnsack O, Nichol G, Humphrey R, Hodi FS (2009) Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin Cancer Res 15:7412–7420PubMedCrossRef
23.
Zurück zum Zitat Weber J (2007) Review: anti-CTLA-4 antibody ipilimumab: case studies of clinical response and immune-related adverse events. Oncologist 12:864–872PubMedCrossRef Weber J (2007) Review: anti-CTLA-4 antibody ipilimumab: case studies of clinical response and immune-related adverse events. Oncologist 12:864–872PubMedCrossRef
25.
Zurück zum Zitat Weber JS, Kahler KC, Hauschild A (2012) Management of immune-related adverse events and kinetics of response with ipilimumab. J Clin Oncol 30:2691–2697PubMedCrossRef Weber JS, Kahler KC, Hauschild A (2012) Management of immune-related adverse events and kinetics of response with ipilimumab. J Clin Oncol 30:2691–2697PubMedCrossRef
26.
Zurück zum Zitat Hutloff A, Dittrich AM, Beier KC, Eljaschewitsch B, Kraft R, Anagnostopoulos I, Kroczek RA (1999) ICOS is an inducible T-cell co-stimulator structurally and functionally related to CD28. Nature 397:263–266PubMedCrossRef Hutloff A, Dittrich AM, Beier KC, Eljaschewitsch B, Kraft R, Anagnostopoulos I, Kroczek RA (1999) ICOS is an inducible T-cell co-stimulator structurally and functionally related to CD28. Nature 397:263–266PubMedCrossRef
27.
Zurück zum Zitat Schenk AD, Gorbacheva V, Rabant M, Fairchild RL, Valujskikh A (2009) Effector functions of donor-reactive CD8 memory T cells are dependent on ICOS induced during division in cardiac grafts. Am J Transplant 9:64–73PubMedCrossRef Schenk AD, Gorbacheva V, Rabant M, Fairchild RL, Valujskikh A (2009) Effector functions of donor-reactive CD8 memory T cells are dependent on ICOS induced during division in cardiac grafts. Am J Transplant 9:64–73PubMedCrossRef
28.
Zurück zum Zitat Yoshinaga SK, Whoriskey JS, Khare SD, Sarmiento U, Guo J, Horan T, Shih G, Zhang M, Coccia MA, Kohno T, Tafuri-Bladt A, Brankow D, Campbell P, Chang D, Chiu L, Dai T, Duncan G, Elliott GS, Hui A, McCabe SM, Scully S, Shahinian A, Shaklee CL, Van G, Mak TW, Senaldi G (1999) T-cell co-stimulation through B7RP-1 and ICOS. Nature 402:827–832PubMedCrossRef Yoshinaga SK, Whoriskey JS, Khare SD, Sarmiento U, Guo J, Horan T, Shih G, Zhang M, Coccia MA, Kohno T, Tafuri-Bladt A, Brankow D, Campbell P, Chang D, Chiu L, Dai T, Duncan G, Elliott GS, Hui A, McCabe SM, Scully S, Shahinian A, Shaklee CL, Van G, Mak TW, Senaldi G (1999) T-cell co-stimulation through B7RP-1 and ICOS. Nature 402:827–832PubMedCrossRef
29.
Zurück zum Zitat An X, Ding PR, Li YH, Wang FH, Shi YX, Wang ZQ, He YJ, Xu RH, Jiang WQ (2010) Elevated neutrophil to lymphocyte ratio predicts survival in advanced pancreatic cancer. Biomarkers 15:516–522PubMedCrossRef An X, Ding PR, Li YH, Wang FH, Shi YX, Wang ZQ, He YJ, Xu RH, Jiang WQ (2010) Elevated neutrophil to lymphocyte ratio predicts survival in advanced pancreatic cancer. Biomarkers 15:516–522PubMedCrossRef
30.
Zurück zum Zitat Sarraf KM, Belcher E, Raevsky E, Nicholson AG, Goldstraw P, Lim E (2009) Neutrophil/lymphocyte ratio and its association with survival after complete resection in non-small cell lung cancer. J Thorac Cardiovasc Surg 137:425–428PubMedCrossRef Sarraf KM, Belcher E, Raevsky E, Nicholson AG, Goldstraw P, Lim E (2009) Neutrophil/lymphocyte ratio and its association with survival after complete resection in non-small cell lung cancer. J Thorac Cardiovasc Surg 137:425–428PubMedCrossRef
31.
Zurück zum Zitat Walsh SR, Cook EJ, Goulder F, Justin TA, Keeling NJ (2005) Neutrophil-lymphocyte ratio as a prognostic factor in colorectal cancer. J Surg Oncol 91:181–184PubMedCrossRef Walsh SR, Cook EJ, Goulder F, Justin TA, Keeling NJ (2005) Neutrophil-lymphocyte ratio as a prognostic factor in colorectal cancer. J Surg Oncol 91:181–184PubMedCrossRef
Metadaten
Titel
Long-term survival and immunological parameters in metastatic melanoma patients who responded to ipilimumab 10 mg/kg within an expanded access programme
verfasst von
Anna Maria Di Giacomo
Luana Calabrò
Riccardo Danielli
Ester Fonsatti
Erica Bertocci
Isabella Pesce
Carolina Fazio
Ornella Cutaia
Diana Giannarelli
Clelia Miracco
Maurizio Biagioli
Maresa Altomonte
Michele Maio
Publikationsdatum
01.06.2013
Verlag
Springer-Verlag
Erschienen in
Cancer Immunology, Immunotherapy / Ausgabe 6/2013
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-013-1418-6

Weitere Artikel der Ausgabe 6/2013

Cancer Immunology, Immunotherapy 6/2013 Zur Ausgabe

Viel pflanzliche Nahrung, seltener Prostata-Ca.-Progression

12.05.2024 Prostatakarzinom Nachrichten

Ein hoher Anteil pflanzlicher Nahrung trägt möglicherweise dazu bei, das Progressionsrisiko von Männern mit Prostatakarzinomen zu senken. In einer US-Studie war das Risiko bei ausgeprägter pflanzlicher Ernährung in etwa halbiert.

Alter verschlechtert Prognose bei Endometriumkarzinom

11.05.2024 Endometriumkarzinom Nachrichten

Ein höheres Alter bei der Diagnose eines Endometriumkarzinoms ist mit aggressiveren Tumorcharakteristika assoziiert, scheint aber auch unabhängig von bekannten Risikofaktoren die Prognose der Erkrankung zu verschlimmern.

Darf man die Behandlung eines Neonazis ablehnen?

08.05.2024 Gesellschaft Nachrichten

In einer Leseranfrage in der Zeitschrift Journal of the American Academy of Dermatology möchte ein anonymer Dermatologe bzw. eine anonyme Dermatologin wissen, ob er oder sie einen Patienten behandeln muss, der eine rassistische Tätowierung trägt.

Erhöhte Mortalität bei postpartalem Brustkrebs

07.05.2024 Mammakarzinom Nachrichten

Auch für Trägerinnen von BRCA-Varianten gilt: Erkranken sie fünf bis zehn Jahre nach der letzten Schwangerschaft an Brustkrebs, ist das Sterberisiko besonders hoch.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.